In general, permeation of drugs through the skin occurs at a very slow rate, if at all. The primary rate limiting step in this process is the passage of compounds through the outermost layer of skin, called the stratum corneum. The stratum corneum is a thin layer of dead cells that acts as an impermeable layer to matter on either side of this layer. The stratum corneum primarily provides the skin's barrier function. It has long been recognized that loss or alteration of the stratum corneum results in increased permeability to many substances; materials can more easily diffuse into or out of the skin. The barrier function of the skin presents a very significant problem to pharmaceutical manufacturers interested in transdermal administration of drugs or in cutaneous collection of bodily fluids.
Transmission and reception of electrical signals and biological materials through human skin is also hindered by the stratum corneum. For example, signal fidelity of bioelectrical potentials and currents measured through skin are degraded by the high impedance of the stratum corneum. Accordingly, the high impedance presents a problem to receiving through the skin the ideal transmission and measurement of bioelectrical signals from human cells, organs, and tissues.
Removal of the stratum corneum reduces the high impedance of the skin and allows better transmission and reception of electrical signals or biological species into and from human tissues. It has also been demonstrated that electromagnetic energy induced alterations of the stratum corneum result in increased permeability to substances (see e.g. U.S. Pat. No. 6,315,722 to Yaegashi, U.S. Pat. No. 6,251,100 to Flock et al., U.S. Pat. No. 6,056,738 to Marchitto et al., and U.S. Pat. No. 5,643,252 to Waner et al.). Alternatively, compounds commonly referred to as “permeation enhancers” can be used, with some success, to penetrate the stratum corneum. Traditional approaches require the abrasion of skin with sand paper and brushes, the stripping of skin with tape and toxic chemicals, the removal of stratum corneum by laser or thermal ablation, or the puncturing of skin with needles. Preparation of skin by these methods may be highly variable, hazardous, painful to the subject, and are generally inconvenient.
Conventional approaches for skin preparation for drug delivery or extraction of analytes through the skin require external feedback mechanism to control the extent of skin preparation. In practice, an electrically conductive coupling medium, a return electrode and/or a hydrogel patch are generally needed to enable the feedback mechanism for controlled skin preparation (see e.g. U.S. Publication No. 20060100567 to Marchitto et al. and U.S. Publication No. 20030204329 to Marchitto et al.). The reliability of such devices and systems can be questionable since the return electrode can provide accurate feedback only when located on a skin site which has sufficient electrical conductivity. Unfortunately, conductivity of the skin varies by a variety of conditions, such as age, location, sun exposure, use of lotions, moisture level, and ambient conditions, etc.
Therefore, an improved system for reducing the high impedance of the skin is needed.
It is an object of the invention to provide an improved system for reducing the high impedance of the skin.
It is a further object of the invention to provide an improved method for measuring the impedance of the skin.
It is yet a further object to provide an improved transdermal drug delivery and/or analyte sensing system.